Document Detail


Anti-inflammatory mechanism of compound K in activated microglia and its neuroprotective effect on experimental stroke in mice.
MedLine Citation:
PMID:  22207656     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Microglial activation plays a pivotal role in the pathogenesis of various neurologic disorders, such as cerebral ischemia, Alzheimer's disease and Parkinson's disease. Thus, controlling microglial activation is a promising therapeutic strategy for such brain diseases. In the present study, we found that a ginseng saponin metabolite, compound K, inhibited the expressions of inducible nitric oxide synthase, proinflammatory cytokines, monocyte chemotactic protein-1, and matrix metalloproteinase-3 and -9 in lipopolysaccharide (LPS)-stimulated BV2 microglial cells and primary cultured microglia. Subsequent mechanistic studies revealed that compound K suppressed microglial activation via inhibiting reactive oxygen species, mitogen-activated protein kinases, and NF-κB/AP-1 activities with enhancement of HO-1/ARE signaling. To address the anti-inflammatory effects of compound K in vivo, we used two brain disease models of mice: sepsis (systemic inflammation) and cerebral ischemia. Compound K reduced the number of Iba1-positive activated microglia and inhibited the expressions of tumor necrosis factor-alpha and interleukin-1 beta in the LPS-induced sepsis brain. Furthermore, compound K reduced the infarct volume of ischemic brain induced by middle cerebral artery occlusion, and suppressed microglial activation in the ischemic cortex. The results collectively suggest that compound K is a promising agent for prevention and/or treatment of cerebral ischemia and other neuroinflammatory disorders.
Authors:
Jin-Sun Park; Jin A Shin; Ji-Sun Jung; Jin-Won Hyun; Thi Kim Van Le; Dong-Hyun Kim; Eun-Mi Park; Hee-Sun Kim
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-29
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  -     ISSN:  1521-0103     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1 Ewha Womans Univeristy Medical School;
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